OrthoSNAP: a tree splitting and pruning algorithm for retrieving single-copy orthologs from gene family trees

Molecular evolution studies, such as phylogenomic studies and genome-wide surveys of selection, often rely on gene families of single-copy orthologs (SC-OGs). Large gene families with multiple homologs in one or more species—a phenomenon observed among several important families of genes such as transporters and transcription factors—are often ignored because identifying and retrieving SC-OGs nested within them is challenging. To address this issue and increase the number of markers used in molecular evolution studies, we developed OrthoSNAP, a software that uses a phylogenetic framework to simultaneously split gene families into SC-OGs and prune species-specific inparalogs. We term SC-OGs identified by OrthoSNAP as SNAP-OGs because they are identified using a <em>s</em>plitti<em>n</em>g <em>a</em>nd <em>p</em>runing procedure analogous to snapping branches on a tree. From 415,129 orthologous groups of genes inferred across seven eukaryotic phylogenomic datasets, we identified 9,821 SC-OGs; using OrthoSNAP on the remaining 405,308 orthologous groups of genes, we identified an additional 10,704 SNAP-OGs. Comparison of SNAP-OGs and SC-OGs revealed that their phylogenetic information content was similar, even in complex datasets that contain a whole genome duplication, complex patterns of duplication and loss, transcriptome data where each gene typically has multiple transcripts, and contentious branches in the tree of life. OrthoSNAP is useful for increasing the number of markers used in molecular evolution data matrices, a critical step for robustly inferring and exploring the tree of life.分子进化研究（如系统发育基因组学研究与全基因组选择压力检测）通常依赖单拷贝直系同源基因簇（single-copy orthologs, SC-OGs）。然而，转运蛋白、转录因子等多个重要基因家族中常存在单个或多个物种携带多份同源拷贝的现象，这类大型基因家族往往被忽视，原因是从中识别并获取嵌套其中的SC-OGs难度极大。为解决这一问题并提升分子进化研究中可用分子标记的数量，我们开发了OrthoSNAP——一款基于系统发育框架的软件，可同时将基因家族拆分为SC-OGs并修剪物种特异性的种内旁系同源基因。我们将OrthoSNAP识别出的SC-OGs命名为SNAP-OGs，因其识别过程采用了类比于修剪树枝的拆分与修剪操作流程。我们在7个真核生物系统发育基因组学数据集中共推断得到415129个基因直系同源簇，从中识别出9821个SC-OGs；针对剩余的405308个基因直系同源簇使用OrthoSNAP进行分析，额外获得了10704个SNAP-OGs。对比SNAP-OGs与SC-OGs的结果显示，二者的系统发育信息含量高度相似，即便在包含全基因组复制、复杂的复制与丢失模式、每个基因通常存在多份转录本的转录组数据，以及生命之树中存在争议分支的复杂数据集里亦是如此。OrthoSNAP有助于提升分子进化数据矩阵中可用标记的数量，这是可靠推断与探索生命之树的关键步骤。